HOXB7 siRNA delivered by hybrid nanoparticles and the co-therapy with tamoxifen: promising strategy against hormone receptor positive breast cancer

Breast cancer is the most common type of cancer that affects and kills women annually in the world. It impacts more than two million women and is responsible for the death of approximately 25% of them. Almost 70% of breast cancer diagnoses are positive for hormone receptor and have a good prognosis. However, resistance to drugs used in hormone therapy, such as tamoxifen, is usual and about 40% of recurrences do not respond to it. In some cases, the overexpression of the HOXB7 gene is related to this mechanism and its silencing can reverse the response to tamoxifen. Here, we used copolymer-coated calcium phosphate nanoparticles to deliver HOXB7 siRNA and restore the sensitization of MCF7 cells to tamoxifen. Nanoparticle synthesis and characterization were performed, and cell viability and gene expression were evaluated. Hybrid nanoparticle presented a Z-average diameter of 83 nm and polydispersity index (PdI) of 0.07, while showing good entrapment of siRNA molecules. We also observed a decrease in HOXB7 gene expression (~65%) promoted by the siRNA molecule delivered by the nanoparticles. The gene silencing has good correlation to the cell viability assay: a reduction in breast cancer viability was observed in 48 (31%) and 72 (38%) hours. As for the co-treatment with tamoxifen, cell viability started dropping after 15 h, which did not occur in the treatment only with Tamoxifen at the same concentration. This result indicates that the biological effect was possibly related to RNAi effect and suggests that HOXB7 may be promoting cell sensitization to tamoxifen without reducing cell viability. Overall, these results suggest that the nanostructured system was effective in promoting gene silencing and that the co-therapy can be a promising tool for the treatment of hormone receptor-positive breast cancers.